tbuckley/cabot-search huggingface dataset:
Doxorubicin-Loaded Polymeric Meshes Prevent Local Recurrence after Sarcoma Resection While Avoiding Cardiotoxicity
Authors: Eric M. Bressler, Ngoc-Quynh Chu, Robert C. Sabatelle, David A. Mahvi, Jenny T. Korunes-Miller, Fumiaki Nagashima, Fumito Ichinose, Rong Liu, Mark W. Grinstaff, Yolonda L. Colson, Chandrajit P. Raut
Journal: Cancer Research (2022)

Surgery is the only potentially curative treatment for localized soft-tissue sarcomas. However, for sarcomas arising in the retroperitoneum, locoregional recurrence rates are 35% to 59% despite resection. Doxorubicin (DOX) is the standard first-line systemic chemotherapy for advanced soft-tissue sarcoma, yet its intravenous administration yields limited clinical efficacy and results in dose-limiting cardiotoxicity. We report the fabrication and optimization of a novel electrospun poly(caprolactone) (PCL) surgical mesh coated with layers of a hydrophobic polymer (poly(glycerol monostearate-co-caprolactone), PGC-C18), which delivers DOX directly to the operative bed following sarcoma resection. In xenograft models of liposarcoma and chondrosarcoma, DOX-loaded meshes (DoM) increased overall survival 4-fold compared with systemically administered DOX and prevented local recurrence in all but one animal. Importantly, mice implanted with DoMs exhibited preserved cardiac function, whereas mice receiving an equivalent dose systemically displayed a 23% decrease from baseline in both cardiac output and ejection fraction 20 days after administration. Collectively, this work demonstrates a feasible therapeutic approach to simultaneously prevent post-surgical tumor recurrence and minimize cardiotoxicity in soft-tissue sarcoma.A proof-of-principle study in animal models shows that a novel local drug delivery approach can prevent tumor recurrence as well as drug-related adverse events following surgical resection of soft-tissue sarcomas.
Optimized User Experience, Efficiency, and Resource Use in Online Self-Management of Atopic Dermatitis
Authors: Dorian Kern, Brjánn Ljótsson, Louise Lönndahl, Erik Hedman-Lagerlöf, Maria Bradley, Nils Lindefors, Martin Kraepelien
Journal: JAMA Dermatology (2022)

This quality improvement study describes the revision of an internet-delivered, self-guided psychological treatment for atopic dermatitis.
Food Insecurity Among Individuals With Cardiovascular Disease and Cardiometabolic Risk Factors Across Race and Ethnicity in 1999-2018
Authors: Eric J. Brandt, Tammy Chang, Cindy Leung, John Z. Ayanian, Brahmajee K. Nallamothu
Journal: JAMA Cardiology (2022)

Food insecurity is a risk factor for poor cardiovascular outcomes that occur disproportionately among individuals from racial and ethnic minority backgrounds who have cardiovascular disease (CVD) or cardiometabolic risk factors.To assess long-term prevalence of food insecurity among those with CVD or cardiometabolic risk factors in the United States.This serial cross-sectional study includes data for noninstitutionalized US adults from the National Health and Nutrition Examination Survey (1999-2018).Food insecurity was assessed using the US Department of Agriculture Adult Food Security Survey Module. We estimated prevalence of food insecurity among adults with prior CVD (myocardial infarction, stroke, heart failure) and cardiometabolic risk factors (hypertension, diabetes, obesity, hyperlipidemia) across racial and ethnic groups and prevalence of Supplemental Nutrition Assistance Program (SNAP) participation among those reporting food insecurity.In the analytic sample of 57 517 adults, 6770 individuals (11.8%) reported food insecurity, which was more prevalent among Hispanic (1938 [24.0%]) and non-Hispanic Black (1202 [18.2%]) than non-Hispanic Asian (100 [8.0%]) and non-Hispanic White adults (3221 [8.5%]). Among 57 517 adults, 4527 (7.9%) had any CVD, 2933 (5.1%) coronary artery disease, 1536 (2.7%) stroke, 1363 (2.4%) heart failure, 28 528 (49.6%) hypertension, 17 979 (33.2%) obesity, 6418 (11.2%) diabetes, and 19 178 (30.8%) dyslipidemia. All CVD and cardiometabolic diseases except coronary artery disease were more prevalent among those with food insecurity. Food insecurity increased over time and was more frequent for patients with CVD but not for cardiometabolic risk factors. From 2011 to 2018, non-Hispanic Black adults with CVD had a decrease in food insecurity prevalence (36.6%; 95% CI, 23.9%-49.4%, to 25.4%; 95% CI, 21.4%-29.3%; P = .04 for trend), whereas adults of other races and ethnicities or data based on cardiometabolic risk factors had no significant change. For individuals who had food insecurity, SNAP participation was higher among those with CVD vs without CVD (54.2%; 95% CI, 46.6%-61.8%, vs 44.3%; 95% CI, 40.5%-48.1%; P = .01).The prevalence of food insecurity among patients with CVD increased over time. Although members of non-Hispanic Black and Hispanic groups had the highest food insecurity, non-Hispanic Black individuals with CVD were the only group to have a significant decrease in food insecurity since 2011. Increased recognition of food insecurity and resources for treating it are needed to address the negative consequences of food insecurity on CVD outcomes.
E-Cigarette Use and Regulation: A Comparative Analysis between the United States, the UK, and China
Authors: Hui Zhang, Yuming Wang, Lijun Shen, Yue Gu, Fengmin Shao
Journal: The American Journal of Bioethics (2022)

This article is referred to by:E-Cigarettes, the FDA, Public Health, and Harm Reduction: A Response to the Open Peer Commentaries
4P Immune checkpoint inhibitors in adrenocortical carcinoma: A meta-analysis
Authors: O. Ababneh, S. Al-Horani, A. Ghazou, M. Alawajneh, B. Shehadeh, O. Kadoumi, S. Alhaj Mohammad, A. Bani-Hani, N. Alrabadi
Journal: Annals of Oncology (2022)
Treatment Utilization and Outcomes for Locally Advanced Rectal Cancer in Older Patients
Authors: Sean Nassoiy, Wade Christopher, Rebecca Marcus, Jennifer Keller, Jessica Weiss, Shu-Ching Chang, Leland Foshag, Richard Essner, Trevan Fischer, Melanie Goldfarb
Journal: JAMA Surgery (2022)

Importance The number of older patients (80 years and older) diagnosed with locally advanced rectal cancer (LARC) is expected to increase. Although current guidelines recommend neoadjuvant chemoradiation therapy (NACRT) followed by resection, little is known about management and outcomes in this older population. Objective To assess the trends in management of older patients diagnosed with LARC who had a surgical resection. Design, Setting, and Participants Patients 80 years and older who had a surgical resection for LARC were identified in the 2004-2016 National Cancer Database. Patients were grouped based on therapy sequence: (1) surgery followed by adjuvant therapy (AT), ie, chemotherapy or radiation; (2) surgery alone; or (3) NACRT followed by surgical resection. Data were analyzed in May 2021. Exposures NACRT followed by surgery, and surgery with or without AT. Main Outcomes and Measures Overall survival (OS) was assessed using Kaplan-Meier analyses with inverse probability of treatment weighting (IPTW) and Cox proportional hazards regression were performed to examine the association of NACRT with the risk of death. Results Of 3868 patients with LARC who underwent surgical resection, 2042 (52.8%) were male, and the mean (SD) age was 83.4 (3.0) years. A total of 2273 (58.8%) received NACRT followed by surgical resection. Factors independently associated with NACRT were more recent diagnosis, age 80 to 85 years (vs 86 years and older), fewer comorbidities, larger tumors, and node-positive disease. The Kaplan-Meier analyses with IPTW showed that 3-year and 5-year OS for NACRT (3-year: 68.9%; 95% CI, 67.0-70.8; 5-year: 51.1%; 95% CI, 49.0-53.4) vs surgery with AT (3-year: 64.4%; 95% CI, 59.0-70.2; 5-year: 43.0%; 95% CI, 37.4-49.5) vs surgery alone (3-year: 55.8%; 95% CI, 52.0-60.0; 5-year: 34.7%; 95% CI, 30.8-39.0) was significantly different ( P &amp;amp;lt; .001). After adjusting for confounders, patients who received NACRT were more likely to undergo an R0 resection (adjusted odds ratio, 2.16; 95% CI, 1.62-2.88), which independently improved OS ( P &amp;amp;lt; .001). Moreover, receipt of NACRT was independently associated with a 25% decreased risk of death (adjusted hazard ratio, 0.75; 95% CI, 0.69-0.82) compared with alternative treatment sequences. Conclusions and Relevance Approximately 40% of older patients with LARC did not receive the current standard of care. In this cohort, NACRT was associated with a higher likelihood of an R0 resection and improved OS. Clinicians should advocate for receipt of NACRT in older patients with LARC.
Distinct Tumor Necrosis Factor Alpha Receptors Dictate Stem Cell Fitness versus Lineage Output in <i>Dnmt3a</i>-Mutant Clonal Hematopoiesis
Authors: Jennifer M. SanMiguel, Elizabeth Eudy, Matthew A. Loberg, Kira A. Young, Jayna J. Mistry, Kristina D. Mujica, Logan S. Schwartz, Timothy M. Stearns, Grant A. Challen, Jennifer J. Trowbridge
Journal: Cancer Discovery (2022)

Clonal hematopoiesis resulting from the enhanced fitness of mutant hematopoietic stem cells (HSC) associates with both favorable and unfavorable health outcomes related to the types of mature mutant blood cells produced, but how this lineage output is regulated is unclear. Using a mouse model of a clonal hematopoiesis-associated mutation, DNMT3AR882/+ (Dnmt3aR878H/+), we found that aging-induced TNFα signaling promoted the selective advantage of mutant HSCs and stimulated the production of mutant B lymphoid cells. The genetic loss of the TNFα receptor TNFR1 ablated the selective advantage of mutant HSCs without altering their lineage output, whereas the loss of TNFR2 resulted in the overproduction of mutant myeloid cells without altering HSC fitness. These results nominate TNFR1 as a target to reduce clonal hematopoiesis and the risk of associated diseases and support a model in which clone size and mature blood lineage production can be independently controlled to modulate favorable and unfavorable clonal hematopoiesis outcomes. Through the identification and dissection of TNFα signaling as a key driver of murine Dnmt3a-mutant hematopoiesis, we report the discovery that clone size and production of specific mature blood cell types can be independently regulated. See related commentary by Niño and Pietras, p. 2724. This article is highlighted in the In This Issue feature, p. 2711.
A Single Nucleotide Polymorphism in <i>SH2B3/LNK</i> Promotes Hypertension Development and Renal Damage
Authors: Matthew R. Alexander, Samuel Hank, Bethany L. Dale, Lauren Himmel, Xue Zhong, Charles D. Smart, Daniel J. Fehrenbach, Yuhan Chen, Nitin Prabakaran, Brian Tirado, Megan Centrella, Mingfang Ao, Liping Du, Yu Shyr, Daniel Levy, Meena S. Madhur
Journal: Circulation Research (2022)

Background: SH2B3 (SH2B adaptor protein 3) is an adaptor protein that negatively regulates cytokine signaling and cell proliferation. A common missense single nucleotide polymorphism in SH2B3 (rs3184504) results in substitution of tryptophan (Trp) for arginine (Arg) at amino acid 262 and is a top association signal for hypertension in human genome-wide association studies. Whether this variant is causal for hypertension, and if so, the mechanism by which it impacts pathogenesis is unknown. Methods: We used CRISPR-Cas9 technology to create mice homozygous for the major (Arg/Arg) and minor (Trp/Trp) alleles of this SH2B3 polymorphism. Mice underwent angiotensin II (Ang II) infusion to evaluate differences in blood pressure (BP) elevation and end-organ damage including albuminuria and renal fibrosis. Cytokine production and Stat4 phosphorylation was also assessed in Arg/Arg and Trp/Trp T cells. Results: Trp/Trp mice exhibit 10 mmHg higher systolic BP during chronic Ang II infusion compared to Arg/Arg controls. Renal injury and perivascular fibrosis are exacerbated in Trp/Trp mice compared to Arg/Arg controls following Ang II infusion. Renal and ex vivo stimulated splenic CD8 + T cells from Ang II-infused Trp/Trp mice produce significantly more interferon gamma (IFNg) compared to Arg/Arg controls. Interleukin-12 (IL-12)-induced IFNg production is greater in Trp/Trp compared to Arg/Arg CD8 + T cells. In addition, IL-12 enhances Stat4 phosphorylation to a greater degree in Trp/Trp compared to Arg/Arg CD8 + T cells, suggesting that Trp-encoding SH2B3 exhibits less negative regulation of IL-12 signaling to promote IFNg production. Finally, we demonstrated that a multi-SNP model genetically predicting increased SH2B3 expression in lymphocytes is inversely associated with hypertension and hypertensive chronic kidney disease in humans.. Conclusions: Taken together, these results suggest that the Trp encoding allele of rs3184504 is causal for BP elevation and renal dysfunction, in part through loss of SH2B3-mediated repression of T cell IL-12 signaling leading to enhanced IFNg production.
2MO EO2401 (EO) therapeutic vaccine for patients (pts) with adrenocortical carcinoma (ACC) and malignant pheochromocytoma/paraganglioma (MPP): Phase I/II SPENCER study
Authors: E. Baudin, S. Grisanti, M. Fassnacht, C.W. Menke-van der Houven van Oordt, H. Haak, C. de la Fouchardiere, V. Subbiah, C. Jimenez, J. Capdevila Castillon, D. Granberg, K.G. Daugaard, M. Kroiss, D. Cosentini, O. Kimpel, L. Lamartina, J. Hadoux, J-M. Paillarse, L. Chêne, J. Fagerberg, A. Berruti
Journal: Annals of Oncology (2022)
Central Cord Syndrome Is Likewise a Surgical Emergency—Time Is Spine
Authors: David O. Okonkwo, Harry M. Mushlin
Journal: JAMA Surgery (2022)

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Remission and Relapse of Dyslipidemia After Vertical Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass in a Racially and Ethnically Diverse Population
Authors: Karen J. Coleman, Anirban Basu, Lee J. Barton, Heidi Fischer, David E. Arterburn, Douglas Barthold, Anita Courcoulas, Cecelia L. Crawford, Benjamin B. Kim, Peter N. Fedorka, Edward C. Mun, Sameer B. Murali, Kristi Reynolds, Robert E. Zane, Sami Alskaf
Journal: JAMA Network Open (2022)

Importance The comparative effectiveness of the most common operations in the long-term management of dyslipidemia is not clear. Objective To compare 4-year outcomes associated with vertical sleeve gastrectomy (VSG) vs Roux-en-Y gastric bypass (RYGB) for remission and relapse of dyslipidemia. Design, Setting, and Participants This retrospective comparative effectiveness study was conducted from January 1, 2009, to December 31, 2016, with follow-up until December 31, 2018. Participants included patients with dyslipidemia at the time of surgery who underwent VSG (4142 patients) or RYGB (2853 patients). Patients were part of a large integrated health care system in Southern California. Analysis was conducted from January 1, 2018, to December 31, 2021. Exposures RYGB and VSG. Main Outcomes and Measures Dyslipidemia remission and relapse were assessed in each year of follow-up for as long as 4 years after surgery. Results A total of 8265 patients were included, with a mean (SD) age of 46 (11) years; 6591 (79.8%) were women, 3545 (42.9%) were Hispanic, 1468 (17.8%) were non-Hispanic Black, 2985 (36.1%) were non-Hispanic White, 267 (3.2%) were of other non-Hispanic race, and the mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 44 (7) at the time of surgery. Dyslipidemia outcomes at 4 years were ascertained for 2168 patients (75.9%) undergoing RYGB and 3999 (73.9%) undergoing VSG. Remission was significantly higher for those who underwent RYGB (824 [38.0%]) compared with VSG (1120 [28.0%]) (difference in the probability of remission, 0.10; 95% CI, 0.01-0.19), with no differences in relapse (455 [21.0%] vs 960 [24.0%]). Without accounting for relapse, remission of dyslipidemia after 4 years was 58.9% (1279) for those who underwent RYGB and 51.9% (2079) for those who underwent VSG. Four-year differences between operations were most pronounced for patients 65 years or older (0.39; 95% CI, 0.27-0.51), those with cardiovascular disease (0.43; 95% CI, 0.24-0.62), or non-Hispanic Black patients (0.13; 95% CI, 0.01-0.25) and White patients (0.13; 95% CI, 0.03-0.22). Conclusions and Relevance In this large, racially and ethnically diverse cohort of patients who underwent bariatric and metabolic surgery in clinical practices, RYGB was associated with higher rates of dyslipidemia remission after 4 years compared with VSG. However, almost one-quarter of all patients experienced relapse, suggesting that patients should be monitored closely throughout their postoperative course to maximize the benefits of these operations for treatment of dyslipidemia.
Development and Comparative Performance of Physiologic Monitoring Strategies in the Emergency Department
Authors: David Kim, Boyang Tom Jin
Journal: JAMA Network Open (2022)

Importance Accurate and timely documentation of vital signs affects all aspects of triage, diagnosis, and management. The adequacy of current patient monitoring practices and the potential to improve on them are poorly understood. Objective To develop measures of fit between documented and actual patient vital signs throughout the visit, as determined from continuous physiologic monitoring, and to compare the performance of actual practice with alternative patient monitoring strategies. Design, Setting, and Participants This cross-sectional study evaluated 25 751 adult visits to continuously monitored emergency department (ED) beds between August 1, 2020, and December 31, 2021. A series of monitoring strategies for the documentation of vital signs (heart rate [HR], respiratory rate [RR], oxygen saturation by pulse oximetry [Sp o 2 ], mean arterial pressure [MAP]) was developed and the strategies’ ability to capture physiologic trends and vital sign abnormalities simulated. Strategies included equal spacing of charting events, charting at variable intervals depending on the last observed values, and discrete optimization of charting events. Main Outcomes and Measures Coverage was defined as the proportion of monitor-derived vital sign measurements (at 1-minute resolution) that fall within the bounds of nursing-charted values over the course of an ED visit (HR ± 5 beats/min, RR ± 3 breaths/min, Sp o 2 ± 2%, and MAP ± 6 mm Hg). Capture was defined as the documentation of a vital sign abnormality detected by bedside monitor (tachycardia [HR &amp;amp;gt;100 beats/min], bradycardia [HR &amp;amp;lt;60 beats/min], hypotension [MAP &amp;amp;lt;65 mm Hg], and hypoxia [Sp o 2 &amp;amp;lt;95%]). Results Median patient age was 60 years (IQR, 43-75 years), and 13 329 visits (51.8%) were by women. Monitored visits had a median of 4 (IQR, 2-5) vital sign charting events per visit. Compared with actual practice, a simple rule, which observes vital signs more frequently if the last observation fell outside the bounds of the previous values, and using the same number of observations as actual practice, produced relative coverage improvements of 31.5% (95% CI, 30.5%-32.5%) for HR, 31.0% (95% CI, 30.0%-32.0%) for MAP, 16.8% (95% CI, 16.0%-17.6%) for RR, and 7.8% (95% CI, 7.3%-8.3%) for Sp o 2 . The same strategy improved capture of abnormalities by 38.9% (95% CI, 26.8%-52.2%) for tachycardia, 38.1% (95% CI, 29.0%-47.9%) for bradycardia, 39.0% (95% CI, 24.2%-55.7%) for hypotension, and 123.1% (95% CI, 110.7%-136.3%) for hypoxia. Analysis of optimal coverage suggested an additional scope for improvement through more sophisticated strategies. Conclusions and Relevance In this cross-sectional study, actual documentation of ED vital signs was variable and incomplete, missing important trends and abnormalities. Alternative monitoring strategies may improve on current practice without increasing the overall frequency of patient monitoring.
Association Between Mental Health Conditions and Postoperative Complications After Gender-Affirming Surgery
Authors: Elizabeth Khusid, Morgan R. Sturgis, Amir H. Dorafshar, Loren S. Schechter, Ephrem O. Olweny, Edward E. Cherullo, Adán Z. Becerra
Journal: JAMA Surgery (2022)

This cohort study assesses whether postoperative complications are associated with having been diagnosed with a mental health condition in patients who have undergone gender-affirming surgery.
25P Identification of novel kinase-activating fusions in non-small cell lung carcinomas (NSCLCs)
Authors: E. Imyanitov, F. Zagrebin, R. Mulkidzhan, E. Krivosheeva, E. Saitova, A.G. Iyevleva, I. Bizin, E. Preobrazhenskaya
Journal: Annals of Oncology (2022)
6P Sensitization of pancreatic and colorectal cancer to radiotherapy, chemotherapy and inhibition of PD-1 expression by newly developed proprotein convertase inhibitors
Authors: S. Pernot, A. François, F. Soulet, G. Desolneux, S. Evrard, G. Siegfried, M. Khatib
Journal: Annals of Oncology (2022)
19P Gene expression profile (GEP) of extensive small-cell lung cancer (eSCLC) patients (pts) receiving first-line platinum-etoposide plus atezolizumab (PEA)
Authors: M. Lorenzi, A. Tosi, G. Crivellaro, S. Frega, A. Ferro, A. Dal Maso, L. Bonanno, A. Rosato, V. Guarneri, G. Pasello
Journal: Annals of Oncology (2022)
10P Sodium selenite presents a great antitumor activity against pancreatic cancer by AIF activation and potentiates gemcitabine by p38 pathway: In vitro and in vivo study
Authors: K. Doello, C. Mesas, G. Perazzoli, L. Cabeza, F. Quiñonero, R. Ortiz
Journal: Annals of Oncology (2022)